Summary of pirfenidone-related adverse event (AE) management strategies

GeneralSlower titration scheduleDose reductions
Dose interruptions
GastrointestinalTaking pirfenidone with a substantial meal, specifically the full dose at the end of a meal or spreading out
during a meal
Dose reductions/interruptions with a slow titration back to full dose
Reduce the morning dose if nausea is experienced at that time of day
Proton-pump inhibitors
SkinContinuous skin protection with clothing and broad-spectrum SPF 50 sunscreen
Avoid use of other medications associated with phototoxicity
With severe phototoxicity, treat with steroids or silver sulfadiazine
Dose reductions for a rash followed by discontinuation if the rash persists and a slow titration back to full dose
Discontinuation if an allergic reaction to pirfenidone occurs
LiverPerform AST, ALT and bilirubin tests before pirfenidone initiation
Monitor at monthly intervals for the first 6 months and then every 3 months thereafter
If AST and ALT elevations (>3× to ≤5× ULN) occur without symptoms or hyperbilirubinaemia, the dose may be reduced or interrupted until values return to normal
If AST and ALT elevations (>3× to ≤5× ULN) are accompanied by hyperbilirubinaemia, permanently discontinue pirfenidone
If patients exhibit >5× ULN, permanently discontinue pirfenidone
Important considerations with drug–drug interactionsFor strong CYP1A2 inhibitors, such as fluvoxamine and enoxacin, pirfenidone should be reduced to 267 mg three times daily (801 mg·day−1)
For moderate CYP1A2 inhibitors, such as ciprofloxacin at a dosage of 750 mg twice daily, pirfenidone should be reduced to 534 mg three times daily (1602 mg·day−1)

SPF: sun protection factor; AST: aspartate transaminase; ALT: alanine transaminase; ULN: upper limit of normal; CYP1A2: cytochrome P450 1A2.